Patsy Ferran and Charlotte Lucas will join the previously announced Douglas Booth and Tony Revolori in the comedy which follows misfit high schoolers as they are brought together by a sex scandal involving one of their teachers.
Ferran's credits include Treasure Island (National Theatre), The Merchant of Venice (RSC) and Blithe Spirit (Gielgud Theatre). Lucas' theatre credits include Red Velvet (Tricycle), Posh (West End and Royal Court Theatre) and Yes, Prime Minister (West End).
Tom Attenborough will direct the piece for Defibrillator, which runs at Trafalgar Studios 2 from 24 February to 1 April.
The piece is Tony Award-winner Karam's first play to be produced in the UK. His work The Humans won the Tony Award for Best Play this year. A film version of Speech and Debate adapted by Karam, will be released in 2017.
Speech and Debate runs at Trafalgar Studios from 24 February to 1 April, with previews from 22 February.